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MR Vol.11 No.2 indexに戻る
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MODERN RHEUMATOLOGY
Vol.11 No.2 |
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Molecular and cellular analyses of HLA class
II-associated susceptibility to autoimmune diseases in the Japanese
population |
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| Y. Nishimura1, H. Ito1, S. Fujii1, H. Tabata1,
Y. Tokano2, Y.-Z. Chen1, I. Matsuda3, H. Mitsuya4, J. Kira5, H.
Hashimoto2, S. Senju1, S. Matsushita1 |
(1)Division of Immunogenetics, Department of
Neuroscience and Immunology, Kumamoto University Graduate School
of Medical Sciences,
2-2-1 Honjo, Kumamoto 860-0811, Japan
(2)Department of Internal Medicine and Rheumatology, Juntendo University School
of Medicine, Tokyo, Japan
(3)Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto,
Japan
(4)Department of Internal Medicine II, Kumamoto University School of Medicine,
Kumamoto, Japan
(5)Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu
University, Fukuoka, Japan |
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| Abstract |
| Abstract It is well known that individuals
who are positive for particular HLA class II alleles show a high
risk of developing autoimmune diseases. HLA class II molecules
expressed on antigen-presenting cells present antigenic peptides
to CD4+ T cells. Their extensive polymorphism affects the structures
of peptides bound to HLA class II molecules to create individual
differences in immune responses to antigenic peptides. In order
to gain a better understanding of mechanisms of the association
between HLA class II alleles and susceptibility to autoimmune diseases,
it is important to identify self-peptides presented by disease-susceptible
HLA class II molecules and triggering disease-causative T cells.
Many of the autoimmune diseases are observed in all ethnic groups,
whereas the incidence of diseases, clinical manifestations and
disease-susceptible HLA class II alleles are different among various
ethnic groups for some autoimmune diseases. These phenomena suggest
that differences in autoimmune self-peptide(s) in the context of
disease-susceptible HLA class II molecules may cause these differences.
Therefore, comparisons among disease-susceptible HLA class II alleles,
autoantigenic peptides, and clinical manifestations of autoimmune
diseases in different ethnic groups would be helpful in elucidating
the pathogenesis of the diseases. In this review, we describe our
recent findings on (1) the uniqueness of both clinical manifestations
and the HLA-linked genetic background of Asian-type (opticospinal
form) multiple sclerosis, (2) the characteristics of glutamic acid
decarboxylase 65 (GAD65) or #2-glycoprotein I (#2-GPI) autoreactive
T cells in Japanese patients with insulin-dependent diabetes mellitus
(IDDM) or anti-#2-GPI antibody-associated autoimmunity, respectively,
and (3) the generation of an efficient delivery system of peptides
to the HLA class II-restricted antigen presentation path-way by
utilizing a class II-associated invariant chain peptide (CLIP)-substituted
invariant chain, which may be applicable to an evaluation of the "molecular
mimicry hypothesis" for the activation of autoreactive T cells. |
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| Key words |
| Key words Autoantigenic peptide ・ Autoimmune
disease ・ Autoreactive T cell ・ Disease susceptibility ・ HLA class
II molecule |
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